Intravenous antioxidant modulation of end-organ damage in L-arginine-induced experimental acute pancreatitis. 2005

J Hardman, and C Shields, and D Schofield, and R McMahon, and H P Redmond, and A K Siriwardena
Department of Academic Surgery, Cork University Hospital and National University of Ireland, Cork, Ireland.

BACKGROUND Oxidative stress mediates acinar injury in experimental acute pancreatitis (AP) and antioxidants are depleted in human AP. This study tests the hypothesis that exogenous antioxidant supplementation ameliorates experimental AP. METHODS Male Sprague-Dawley rats were randomly allocated to 1 of 4 groups (n = 5/group) and sacrificed at 72 h. AP was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/l sodium chloride. Group allocations were: group 1 (control) no intervention; group 2 AP; group 3 early multiple antioxidant (MAOX) intervention comprising 15 microg/kg selenium, 30 microg/kg ascorbate and 300 mg/kg N-acetylcysteine given at 6 and 30 h and group 4 the MAOX combination above given at 24 and 48 h. Endpoints were: serum amylase, antioxidant levels, bronchoalveolar lavage (BAL) protein and lung myeloperoxidase (MPO) activity and histological assessment of pancreatic injury. RESULTS L-arginine induced AP characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Early MAOX reduced pulmonary MPO and BAL protein and reduced acinar swelling, degranulation and pancreatic parenchymal infiltration by inflammatory cells. These features were absent when intervention was delayed. CONCLUSIONS In this model, early but not late antioxidant intervention ameliorates pancreatic and pulmonary injury.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009195 Peroxidase A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. Myeloperoxidase,Hemi-Myeloperoxidase,Hemi Myeloperoxidase
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D010195 Pancreatitis INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis. Acute Edematous Pancreatitis,Acute Pancreatitis,Pancreatic Parenchyma with Edema,Pancreatic Parenchymal Edema,Pancreatitis, Acute,Pancreatitis, Acute Edematous,Peripancreatic Fat Necrosis,Acute Edematous Pancreatitides,Acute Pancreatitides,Edema, Pancreatic Parenchymal,Edematous Pancreatitides, Acute,Edematous Pancreatitis, Acute,Fat Necrosis, Peripancreatic,Necrosis, Peripancreatic Fat,Pancreatic Parenchymal Edemas,Pancreatitides, Acute,Pancreatitides, Acute Edematous,Parenchymal Edema, Pancreatic,Peripancreatic Fat Necroses
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug

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